Pseudotyping lentiviral vectors with the wild-type measles virus glycoproteins improves titer and selectivity

Funke, Sabrina; Schneider, Irene C.; Glaser, Stefanie; Mühlebach, Michael D.; Möritz, Thomas; Cattaneo, Roberto; Cichutek, Klaus; Buchholz, CJ

doi:10.1038/gt.2009.11

Cited by 55 publications

(41 citation statements)

References 25 publications

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“…The pseudotyping with vesicular stomatitis virus glycoprotein (VSV-G) as a viral envelope protein has broadened the natural tropism of the virus to infect basically all human and murine cell types (Burns et al, 1993). Using various viral envelopes, the recombinant viruses can be introduced into different target cells, including lymphocytes and nerve cells (Colin et al, 2009;Funke et al, 2009;Miletic et al, 2004). Some viruses have two envelope proteins with distinct functions, to bind to the host receptor and to fuse with the membrane for entry ).…”

Section: Specific Delivery Of Transgenes To Target Cellsmentioning

confidence: 99%

Effective Transgene Constructs to Enhance Gene Therapy with Trichostatin A

Hayashi¹,

Ma²,

Kohno³

et al. 2011

Targets in Gene Therapy

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Section: Specific Delivery Of Transgenes To Target Cellsmentioning

confidence: 99%

Effective Transgene Constructs to Enhance Gene Therapy with Trichostatin A

Hayashi¹,

Ma²,

Kohno³

et al. 2011

Targets in Gene Therapy

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“…We have previously shown that a lentiviral vector pseudotyped with the measles virus glycoproteins displaying a CD20-specific scFv forms multiple contacts with CD20, thereby triggering mitotic activation in resting lymphocytes (44,45). It is well conceivable that also MV-141.7 establishes multiple scFv-CD133 contacts on the tumor cell surface.…”

Section: Discussionmentioning

confidence: 99%

Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus

et al. 2013

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Tumor-initiating cells (TIC) are critical yet evasive targets for the development of more effective antitumoral strategies. The cell surface marker CD133 is frequently used to identify TICs of various tumor entities, including hepatocellular cancer and glioblastoma. Here, we describe oncolytic measles viruses (MV) retargeted to CD133. The viruses, termed MV-141.7 and MV-AC133, infected and selectively lysed CD133 þ tumor cells. Both viruses exerted strong antitumoral effects on human hepatocellular carcinoma growing subcutaneously or multifocally in the peritoneal cavity of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Notably, the CD133-targeted viruses were more effective in prolonging survival than the parental MV-NSe, which is currently assessed as oncolytic agent in clinical trials. Interestingly, target receptor overexpression or increased spreading kinetics through tumor cells were excluded as being causative for the enhanced oncolytic activity of CD133-targeted viruses. MV-141.7 was also effective in mouse models of orthotopic glioma tumor spheres and primary colon cancer. Our results indicate that CD133-targeted measles viruses selectively eliminate CD133 þ cells from tumor tissue, offering a key tool for research in tumor biology and cancer therapy. Cancer Res; 73(2); 865-74. Ó2013 AACR.

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“…As shown in Figure 1C, OKT8 dramatically reduced CD8-LV-mediated transduction in a concentration-dependent manner, whereas the addition of isotype control antibody had no effect. Moreover, the presence of OKT8 did not influence transduction mediated by MV-LV, 25 carrying nonblinded MV glycoproteins, or VSV-G-LV. This result demonstrates that transduction mediated by CD8-LV was because of the displayed scFv.…”

Section: Generation and Characterization Of Cd8-lvmentioning

confidence: 99%

T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing

Zhou

Schneider

Edes

et al. 2012

Blood

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Transfer of tumor-specific T-cell receptor (TCR) genes into patient T cells is a promising strategy in cancer immunotherapy. We describe here a novel vector (CD8-LV) derived from lentivirus, which delivers genes exclusively and specifically to CD8 ؉ cells. CD8-LV mediated stable in vitro and in vivo reporter gene transfer as well as efficient transfer of genes encoding TCRs recognizing the melanoma antigen tyrosinase. Strikingly, T cells genetically modified with CD8-LV killed melanoma cells reproducibly more efficiently than CD8 ؉ cells transduced with a conventional lentiviral vector. Neither TCR expression levels, nor the rate of activation-induced death of transduced cells differed between both vector types. Instead, CD8-LV transduced cells showed increased granzyme B and perforin levels as well as an up-regulation of CD8 surface expression in a small subpopulation of cells. Thus, a possible mechanism for CD8-LV enhanced tumor cell killing may be based on activation of the effector functions of CD8 ؉ T cells by the vector particle displaying OKT8-derived CD8-scFv and an increase of the surface density of CD8, which functions as coreceptor for tumor-cell recognition. CD8-LV represents a powerful novel vector for TCR gene therapy and other applications in immunotherapy and IntroductionIn the human body, a vast diversity of immune cells constantly patrols the blood stream and tissues to protect from invaders. Each type of these immune cells fulfills different functions. Genetic modification of these cells is a key technology to elucidate their physiologic functions and to develop novel therapeutic strategies. Among the different types of gene vector systems available, ␥-retroviral and lentiviral vectors (LVs) have become state-of-theart technology for lymphocyte gene transfer. [1][2][3] Failure to distinguish between subtypes of cells and thereby transferring genes to both target and nontarget cells is a limitation of vector systems currently in use. Selective and specific delivery of transgenes into particular types of lymphocytes is highly desirable for immunotherapy and gene therapy. Although few attempts have been undertaken to retarget LVs to CD3 ϩ T cells, 4 the transduction of subpopulations or even the transfer of therapeutic genes by such targeting vectors has not been described. In addition, no targeting vector specific for CD8 ϩ T cells has been described. CD8 ϩ T cells are among the most important immune cell types and also a primary target for immunotherapy because of their capacity to directly engage and kill pathogen infected cells or tumor cells. 5 Adoptive transfer of tumor-specific T cells is a promising strategy of directed tumor cell killing, which is currently under investigation in clinical trials worldwide. 6-9 Tumor specificity is provided by an antigen receptor, which can be natural (T-cell receptor; TCR) or engineered (chimeric antigen receptor, CAR). Whereas TCR gene-modified T cells recognize peptide-major histocompatibility complex (pMHC), CAR recognize antigen in an MHC-independen...

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Pseudotyping lentiviral vectors with the wild-type measles virus glycoproteins improves titer and selectivity

Cited by 55 publications

References 25 publications

Effective Transgene Constructs to Enhance Gene Therapy with Trichostatin A

Effective Transgene Constructs to Enhance Gene Therapy with Trichostatin A

Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus

T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing

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